The increase in polydrug abuse of agents such as tetrahydrocannabinol (THC, active ingredient of marihuana), phencyclidine (PCP), methaqualone (MQ), cocaine, alcohol, and others has resulted in a number of drug interactions, the clinical recognition and management of which has constantly challenged the medical community. Although much is known about the pharmacology of these agents, it is not clear whether these interactions occur at the dispositional/metabolic level or are due to functional changes in the user. Therefore, the purpose of this investigation is to elucidate the mechanisms for or types of drug interactions involving THC, PCP and MQ. To accomplish this, male rats will be treated with combinations of THC and radiolabeled PCP or MQ. Six types of studies will be conducted to determine the effects of THC pretreatment on the following pharmacologic characteristics of PCP and MQ: plasma disappearance; distribution in brain, liver, lung, kidney, testis and adipose tissue; biliary, urinary, and fecal excretion; metabolism; protein binding; and toxicity (ED50, LD50). Comparisons will be made in these various studies between groups which were treated with PCP or MQ alone or in combination with THC. Methods utilized in these studies will include various radioisotope techniques, extraction and purification procedures, and thin layer chromatography. The results of these studies should help identify the mechanisms of drug interactions involving THC, PCP and MQ. This information will not only enlarge our knowledge about the pharmacology of these agents, but should also aid in the identification and treatment of serious interactions resulting from their abuse.